| Autor: |
Holgersen MG; Copenhagen University Hospital, Rigshospitalet, Danish PCD Centre, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen, Denmark; mathias.geldermann.holgersen.01@regionh.dk., Marthin JK; Copenhagen University Hospital, Rigshospitalet, The Danish PCD Centre, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen, Denmark., Raidt J; University Children's Hospital Muenster, Department of General Paediatrics, Muenster, Germany.; The primary ciliary dyskinesia clinical trial network (PCD-CTN), Muenster, Germany.; European Reference Network for respiratory Diseases (ERN-LUNG), Muenster, Germany., Qvist T; Copenhagen University Hospital, Rigshospitalet, Danish PCD Centre, Department of Infectious Diseases, Copenhagen, Denmark., Johansen HK; Copenhagen University Hospital, Rigshospitalet, Department of Clinical Microbiology, Copenhagen, Denmark.; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark., Omran H; University Children's Hospital Muenster, Department of General Paediatrics, Muenster, Germany.; The primary ciliary dyskinesia clinical trial network (PCD-CTN), Muenster, Germany.; European Reference Network for respiratory Diseases (ERN-LUNG), Muenster, Germany., Nielsen KG; Copenhagen University Hospital, Rigshospitalet , Danish PCD Centre, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen, Denmark.; The primary ciliary dyskinesia clinical trial network (PCD-CTN), Copenhagen, Denmark.; European Reference Network for respiratory Diseases (ERN-LUNG), Copenhagen, Denmark.; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark. |
| Abstrakt: |
Rationale: Primary ciliary dyskinesia is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives: We aimed to explore long-term lung function in primary ciliary dyskinesia grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa . Methods: In this retrospective, observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated FEV 1 z-score trends and compared them at ages 10, 25, and 50 years, while Generalized Estimating Equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Measurements and Main Results: We included 127 genotyped subjects, 6,691 spirometries and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early onset and sustained decline in lung function, while DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures were on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa . Conclusion: Long-term lung function in primary ciliary dyskinesia follows discrete genotype specific profiles and appear independent of P. aeruginosa infection. We confirm and extend previous findings of CCDC39 and CCDC4 0 as variants associated with early onset severe lung function impairment persisting in the long term. |
